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  • 1
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 607-607
    Abstract: We treated 520 patients ≤60 years with de novo (n=414) or secondary (n=106) AML. Patients with CBF-leukemias [t(8;21) or inv(16)] or normal karyotype and good response (GR) to induction I (≤5% blasts in d15 BM) were considered standard risk (SR), all others as high risk (HR). Patients with t(15;17) were excluded. Induction I consisted of standard dose araC, idarubicine and etoposide (IVA-I). Patients with GR to IVA-I continued with IVA–II on d21. In patients with bad response ( & gt;5% BM blasts on d15), the second cycle consisted of either IVA–II or FlAG/Ida. Induction was followed by early consolidation with intermediate dose araC. As late consolidation, SR patients with normal karyotype and an HLA-matched sibling received matched related donor (MRD) transplantation. The remaining SR patients were randomized between high dose (HD) araC (12 x 3g/m2)/daunorubicine (3 x 45mg/m2) or an autologous peripheral blood stem cell transplantation (autoPBCSCT) with PBSC mobilized after early consolidation. 90% of the 262 SR patients achieved CR in contrast to only 59% of the 249 HR patients (overall CR rate 74%). After 75 months, overall survival (OS) and relapse free survival (RFS) was significantly better for SR than for HR patients. Within the SR group, OS for patients with CBF leukemia (n=62) at 56 months was significantly better than for patients with normal karyotype (n=200). RFS was similar for both groups. 57 SR patients (14 with CBF leukemia) were randomized to receive HD araC and 62 (16 with CBF leukemia) to undergo autoPBSCT. At 70 months, OS and RFS was not different for the patients treated with autoPBSCT and for those receiving HD araC. This was true for patients with normal karyotype as well as CBF leukemias. Median duration of neutropenia ( & lt;500/μl) was 9 days for autoPBSCT and 19 days for HD araC (p & lt;0.01) with a significantly higher rate of septicemia (21% vs. 11%) and pneumonia (14% vs. 3%) after HD araC. Duration of thrombocytopenia was 21 days for HD araC and 11 days for autoPBSCT (p & lt;0.01). In SR patients with normal karyotype, OS and RFS after MRD transplantation did not significantly differ from HD araC or autoPBSCT. However, when looking at the FLT3 status in patients with normal karyotype (n=49), chemoconsolidation resulted in an inferior survival (17%) in patients with mutated FLT3 as compared to autotransplantation (67%). In conclusion, outcome is similar in SR AML patients after autoPBSCT, HD araC or MRD transplantation. In SR patients without an HLA-identical sibling donor, autoPBSCT instead of HD araC as used in our study is recommended for late consolidation due to the reduced treatment related toxicity and should be studied prospectively in patients with mutated FLT3.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 2
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 433-433
    Abstract: In this prospective multicenter trial, we treated 520 patients with AML ≤60 years (414 with de novo and 106 with secondary AML). Patients with CBF-leukemias [t(8;21) or inv(16)] or normal karyotype and good response (GR) to induction I (≤5% blasts in day 15 BM) were considered standard risk (SR), all other patients as high risk (HR). Patients with t(15;17) were excluded. Induction course I consisted of standard dose araC, idarubicine and etoposide (IVA-I). Patients with GR to IVA-I continued with IVA-II on day 21. In patients with bad response (BR; & gt;5% BM blasts on day 15), the second cycle consisted of either IVA-II or FlAG/Ida. Double induction was followed by early consolidation with intermediate dose araC. As late consolidation, HR patients with an HLA-matched sibling were scheduled for a matched related donor (MRD) transplantation; patients without a family donor should undergo autologous peripheral blood stem cell transplantation (autoPBSCT). PBSC were mobilized after early consolidation. An interim analysis showed superior results for allogeneic transplants compared to patients who had undergone autoPBSCT. Therefore, since 2003 all HR patients without a sibling donor were scheduled for matched unrelated donor (MUD) transplantation. 147 of 249 HR patients (59%) achieved complete remission. 33 (13%) of the HR patients died during induction. After 75 months, overall survival (OS) was significantly worse for HR patients (24%) than for SR patients (53%). For HR patients, there was no difference in OS and relapse-free survival (RFS) between patients classified as HR because of BR to IVA-1 (n = 83), unfavourable karyotype (n = 87) or both characteristics (n = 79). RFS was neither different between HR patients with de novo or secondary AML nor between HR patients with normal karyotype, complex karyotype or other high risk cytogenetics. Regarding late consolidation, the “as treated” analysis revealed that OS and RFS was significantly better after an MRD transplantation (n=41, OS 67%, RFS 62%) than after autoPBSCT (n=27, OS 14%, RFS 7%). Patients who received a MUD transplantation (n=32) showed a significantly better RFS (52%) than after autoPBSCT. RFS and OS after MUD transplantation did not differ significantly from MRD transplants. OS of patients after autoPBSCT was not significantly different from patients who received no transplant at all after entering CR. Of the 69 HR patients who did not enter CR after induction, 44 received an MRD or MUD transplantation. 15 of these patients (35%) are alive in CR. In conclusion, HR patients as defined in our study do not benefit from an autologous PBSCT and an allogeneic MRD or MUD transplantation should be performed. Moreover, allogeneic transplants are a viable salvage option for HR patients not entering CR.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 3
    Online Resource
    Online Resource
    Elsevier BV ; 1983
    In:  The American Journal of Medicine Vol. 75, No. 5 ( 1983-11), p. 65-69
    In: The American Journal of Medicine, Elsevier BV, Vol. 75, No. 5 ( 1983-11), p. 65-69
    Type of Medium: Online Resource
    ISSN: 0002-9343
    Language: English
    Publisher: Elsevier BV
    Publication Date: 1983
    detail.hit.zdb_id: 2003338-2
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  • 4
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 1719-1719
    Abstract: Abstract 1719 Acute myeloblastic leukemia with normal karyotype (CN-AML) is a heterogenous disease. During the past years, a wide variety of somatic gene mutations has been described in these patients. For several of these mutations, a prognostic impact in first-line therapy of patients with CN-AML has clearly been established in numerous large studies. In contrast, data on the influence of these aberrations on outcome after relapse are limited. We analyzed 98 adult patients up to 60 years of age (median age 47 years) with CN-AML in first relapse for clinical and molecular risk factors for survival. All patients were treated within two prospective multicenter trials. First-line treatment consisted of double induction and intensive consolidation therapy with high dose cytarabine, autologous or allogeneic stem cell transplantation. Leukemic blasts were analyzed for genetic aberrations in the genes FLT3, NPM1, CEBPA, WT1, IDH1 and IDH2. Median duration of first CR was 9.1 months. 33% of the patients had an FLT3-ITD, 50% a mutation in NPM1, 8% in CEBPA, 11% in WT1, 12% in IDH1 and 11% in IDH2. 28% had the genotype NPM1mutated/FLT3-ITDnegative. Seventy-seven of the patients received intensive re-induction chemotherapy after relapse, 17 patients directly received an allogeneic stem cell transplantation and only four patients received no further intensive treatment. A second CR was achieved in 52% of the 77 patients with re-induction. Presence of an FLT3-ITD (OR 0.24; 95% CI 0.07 – 0.80), duration of CR1 〈 6 months (OR 0.24; 95% CI 0.06 – 0.92) and age above 47 years (OR 0.31; 95% CI 0.10 – 0.98) were associated with significantly inferior CR2 rates. Median survival after relapse was 9.7 months and six-year survival was 27%. In multivariate analysis, age above 47 years (HR 2.66, 95% CI 1.55 – 4.55) and FLT3-ITD (HR 2.06; 95% CI 1.22 – 3.94) were the only independent prognostic factors for survival. Other clinical or molecular parameters had no impact on survival. Patients with none of these risk factors (n = 27) had a six-year survival of 54%. In patients with one (n = 43) or both (n = 18) of these factors, survival was significantly inferior (15% and 6% six-year survival respectively). This was even true when only patients were considered who received an allogeneic stem cell transplantation after relapse (n = 51). In these patients, six-year survival was 64% when none of these risk factors was present, 24% for one risk factor and 20% for patients with both factors. In conclusion, FLT3-ITD and older age are the major prognostic factors in relapsed CN-AML. Patients with none of these factors have a relatively good outcome after re-induction and allogeneic stem cell transplantation. In contrast, patients with at least one of these risk factors have a dismal prognosis and might be considered for investigational treatment approaches after relapse. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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